Protection against Aerosolized Yersinia pestis Challenge following Homologous and Heterologous Prime-Boost with Recombinant Plague Antigens

Abstract

A Yersinia pestis-derived fusion protein (F1-V) has shown great promise as a protective antigen against aerosol challenge with Y. pestis in murine studies. In the current study, we examined different prime-boost regimens with F1-V and demonstrate that (i) boosting by a route other than the route used for the priming dose (heterologous boosting) protects mice as well as homologous boosting against aerosol challenge with Y. pestis, (ii) parenteral immunization is not required to protect mice against aerosolized plague challenge, (iii) the route of immunization and choice of adjuvant influence the magnitude of the antibody response as well as the immunoglobulin G1 (IgG1)/IgG2a ratio, and (iv) inclusion of an appropriate adjuvant is critical for nonparenteral immunization.Recently, a great deal of attention has been directed towards needle-free immunization strategies as alternative methods for vaccine delivery. Both mucosal (intranasal [i.n.], oral, and rectal) and transcutaneous (t.c.) immunization in the presence of an appropriate adjuvant have been shown to induce humoral and cellular immune responses in both the systemic and mucosal compartments of immunized animals. Alternating routes for delivery of the priming dose and booster dose in immunizations, so-called prime-boost strategies, have also been examined. Such prime-boost strategies could be particularly important in an imminent or postrelease bioterrorism event if it is possible to administer a parenteral priming dose and, at the same time, distribute a follow-up patch, pill, or nasal applicator that could be self administered. Such vaccine strategies would greatly improve national preparedness.In a recent study, we evaluated different prime-boost regimens, including parenteral, mucosal, and transcutaneous delivery, in order to explore the effect of changing the route of prime and boost on the ability of the recombinant Yersinia pestis-derived fusion protein (F1-V) to promote the development of long-lasting, high-titer antibodies (13). F1-V has been shown to provide protection against flea-borne, subcutaneous (s.c.), and aerosol challenge and has the potential to provide protective immunity against pneumonic as well as bubonic plague due to either wild-type F1 ϩ Y. pestis or to naturally occurring F1 Ϫ variants (16, 17). The most significant finding of our previous study is that boosting by a different (heterologous) route than the priming dose can be as effective as or more effective than homologous boosting for induction of either serum or bronchoalveolar anti-F1-V immunoglobulin G1 (IgG1) responses.In the current study, we examined the abilities of different prime-boost regimens with recombinant F1-V to protect mice against aerosol challenge with Y. pestis. We also examined the role of the coadministered adjuvant in inducing protection. For parenteral immunization, mice were immunized s.c. with 10 g of F1-V alone or adsorbed to alum adjuvant (2.0% Alhydrogel, batch no. 3275; Superfos Biosector, Vedbaek, Denmark) brought to a final volume of 100 l with ...

Effect of adjuvants and route of immunizations on the immune response to recombinant plague antigens

“…However, adjuvants do more than just increase the magnitude of the immune response and the qualitative nature of the response is also important. We recently demonstrated that SC immunization with F1-V in the absence of an adjuvant can confer 70% protection against aerosol challenge with Y. pestis [13]. However, IN immunization in the absence of adjuvant resulted in 100% mortality while the inclusion of adjuvant in the formulation provided 90% protection, demonstrating that an adjuvant is necessary for protection following IN immunization.…”

“…The most significant finding of that study is that boosting by a different (heterologous) route than the priming dose can be as or more effective than homologous boosting for induction of either serum or bronchioalveolar anti-F1-V IgG1 responses. In a follow-on aerosol challenge study [13], we demonstrated that the route of immunization and choice of adjuvant influence the magnitude of the antibody response as well as the IgG1/IgG2a ratio, and that inclusion of an appropriate adjuvant in the vaccine formulation is critical for protection against aerosol challenge following non-parenteral immunization.…”

Effective Plague Vaccination via Oral Delivery of Plant Cells Expressing F1-V Antigens in Chloroplasts

“…It is becoming increasingly clear that mixing of vaccine routes can have a positive effect on both antibody production and protection. It has been previously reported that in F1-V vaccinations, heterologous prime-boost regimens are at least as effective as homologous boost regimens for inducing serum anti-F1-V IgG1 responses (29,30). In this study, all vaccinated mice received an initial s.c. injection, which effectively induced a potent systemic humoral response (Fig.…”

Intranasal Immunization of Mice with a Bovine Respiratory Syncytial Virus Vaccine Induces Superior Immunity and Protection Compared to Those by Subcutaneous Delivery or Combinations of Intranasal and Subcutaneous Prime-Boost Strategies

“…delivered FI-BRSV vaccine in mice (32). Since there is evidence that combinations of mucosal and parenteral administration lead to immune responses that were as strong or stronger than those resulting from either mucosal or parenteral immunization alone (21,22,29,30), the purpose of this study was to determine the effects of the route of delivery on antibody, mucosal, and cell-mediated immune responses, as well as protection against BRSV. We compared i.n.…”